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Abstract Details

APOE e4 Linked Effects on Neuropathology and Clinical Features in Dementia with Lewy Bodies
Aging, Dementia, and Behavioral Neurology
S1 - Innovations in Non-AD Dementia (2:36 PM-2:48 PM)
009
APOE e4 is a known genetic factor affecting Alzheimer’s disease (AD) risk. Alzheimer’s pathology is commonly observed in DLB and is associated with worse functional cognition and faster memory decline. It remains uncertain whether APOE e4 independently contributes to Lewy body pathology, and whether Alzheimer’s co-pathology contributes to the core clinical features of DLB.
We aimed to assess APOE e4-associated effects on α-synuclein pathology and Alzheimer’s co-pathology in dementia with Lewy bodies (DLB), and to explore the impact of APOE e4 on DLB-specific clinical features, including fluctuating cognition, visual hallucinations, rapid eye movement sleep behavior disorder (RBD) and parkinsonism.
A total of 38,414 participants, composed of 1,170 DLB, 1,032 Parkinson's disease (PD), 17,416 AD and 18,796 controls (CN), were included in this study. Logistic regression was applied to examine the relation between neuropathology and APOE genotype, and to assess the relation between APOE genetic risk score and the four core clinical features.
APOE e4 was associated with more severe Lewy body pathology in participants with not or low AD neuropathologic change (OR: 1.39, 95%CI: 1.01, 1.94, p = 0.049). Two-thirds of DLB participants developed fluctuating cognition, visual hallucinations, or RBD, more than in PD, AD, and CN groups. 86.9% of DLB participants developed parkinsonism, which was significantly higher than in AD and CN groups. The risk of developing fluctuating cognition decreased with increased APOE genetic risk score (OR: 0.72, 95%CI: 0.53, 0.97, p = 0.031). Similar patterns were observed for RBD and parkinsonism. In contrast, the risk of developing visual hallucinations increased with increased APOE genetic risk score (OR: 1.16, 95%CI: 1.12, 1.20, p < 0.001). 
An association appears to exist between APOE e4 and Lewy body pathology that is independent of the severity of Alzheimer’s pathology. The core clinical features of LBD are sensitive to APOE e4 haplotype.
Authors/Disclosures
Rong Ye, MD, PhD (Massachusetts General Hospital)
PRESENTER 		Dr. Ye has nothing to disclose.
Anna Goodheart, MD (Massachusetts General Hospital, Harvard) The institution of Dr. Goodheart has received research support from 好色先生.
Erin Peterec, BA (Massachusetts General Hospital) Ms. Peterec has nothing to disclose.
Stephen N. Gomperts, MD, PhD, FAAN (Massachusetts General Hospital) Dr. Gomperts has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EIP. Dr. Gomperts has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cowen. Dr. Gomperts has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bob's Last Stand. Dr. Gomperts has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Focus Boston. Dr. Gomperts has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Expert connect. Dr. Gomperts has received personal compensation in the range of $0-$499 for serving as a Consultant for Mosaic. Dr. Gomperts has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jannsen. The institution of Dr. Gomperts has received research support from NIH. The institution of Dr. Gomperts has received research support from LBDA. The institution of Dr. Gomperts has received research support from DOD/CDMRP. The institution of Dr. Gomperts has received research support from FFFPRI. The institution of Dr. Gomperts has received research support from NIH. The institution of Dr. Gomperts has received research support from MJFF. The institution of Dr. Gomperts has received research support from NIH. The institution of Dr. Gomperts has received research support from NIH. The institution of Dr. Gomperts has received research support from MJFF. The institution of Dr. Gomperts has received research support from NIH. The institution of Dr. Gomperts has received research support from NIH. Dr. Gomperts has received intellectual property interests from a discovery or technology relating to health care.